1. Field of the Invention
This invention relates to indomethacin, a relatively new compound that has found wide use as an anti-inflammatory agent, an antipyretic and an analgesic. More particularly, the invention relates to the elimination of the undesirable gastric side effects caused by the compound.
2. The Prior Art
Non-steroidal anti-inflammatory agents, such as aspirin and indomethacin, have long been known to be ulcerogenic, particularly in conjunction with other influences, such as stress. One of the most successful efforts to combat this undesirable side effect of an otherwise very useful compound has been the use of metiamide with aspirin, disclosed by Brown et al. in "Histamine H.sub.2 Receptor: Involvement in Gastric Ulceration," Life Sciences 18, pages 339-344 (Pergamon Press, 1976). Interestingly, this compound metiamide, which was found to reliably reduce ulceration produced by stress alone, or by a combination of stress and aspirin, is known to be an H.sub.2 histamine receptor antagonist. On the other hand, H.sub.1 receptor antagonists, such as pyrilamine and promethazine, compounds which have been heretofore administered with aspirin for purposes other than that of present concern, have been found by the same workers to be ineffective for the control of gastric ulceration.
As to indomethacin, attempts to combat the gastrointestinal side effects that it induces in a patient have resulted in the discovery that the undesirable effects can be controlled by the administration of certain prostaglandin substances (Lippmann, U.S. Pat. No. 3,927,213) and certain amino acids (Takagi et al., U.S. Pat. No. 3,988,466). It should be noted also that indomethacin itself can be used to control, inter alia, the peptic ulcer complications often produced by anti-inflammatory adrenocortical steroids (Winter, U.S. Pat. No. 3,461,208).